15 results on '"Lesne, Elodie"'
Search Results
2. Generation of a Universal Human Complement Source by Large-Scale Depletion of IgG and IgM from Pooled Human Plasma
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Alexander, Frances, primary, Brunt, Emily, additional, Humphries, Holly, additional, Cavell, Breeze, additional, Leung, Stephanie, additional, Allen, Lauren, additional, Halkerston, Rachel, additional, Lesne, Elodie, additional, Penn, Elizabeth, additional, Thomas, Stephen, additional, Gorringe, Andrew, additional, and Taylor, Stephen, additional
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- 2021
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3. 84 Inhibition of SARS-CoV-2 spike interaction with angiotensin converting enzyme-2 (ACE2) by specific antibodies is enhanced by complement, determined with a novel flow cytometry assay
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McStraw, Nikki, primary, Lesne, Elodie, additional, Cavell, Breeze, additional, Leung, Stephaine, additional, Taylor, Stephen, additional, and Gorringe, Andrew, additional
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- 2023
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4. Structural insight into the role of the PAS domain for signal transduction in sensor-kinase BvgS
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Dupré, Elian, Clantin, Bernard, Yuan, Youhua, Lecher, Sophie, Lesne, Elodie, Antoine, Rudy, Villeret, Vincent, Jacob-Dubuisson, Françoise, Jacob-Dubuisson, Françoise, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)
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PAS domain ,PAS domain of BvgS Two-component system ,[SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,[SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM] ,sensor-kinases ,[SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,virulence regulation ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Bordetella pertussis - Abstract
International audience; The two-component system BvgAS controls the virulence regulon in Bordetella pertussis. BvgS is the prototype of a family of sensor histidine-kinases harboring periplasmic Venus flytrap (VFT) domains. The VFT domains are connected to the cytoplasmic kinase moiety by helical linkers separated by a Per-ARNT-Sim (PAS) domain. Antagonism between the two linkers, as one forms a coiled coil when the other is dynamic and vice versa, regulates BvgS activity. Here we solved the structure of the intervening PAS domain by X-ray
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- 2021
5. Acellular Pertussis Vaccines Induce Anti-pertactin Bactericidal Antibodies Which Drives the Emergence of Pertactin-Negative Strains
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Lesne, Elodie, primary, Cavell, Breeze E., additional, Freire-Martin, Irene, additional, Persaud, Ruby, additional, Alexander, Frances, additional, Taylor, Stephen, additional, Matheson, Mary, additional, van Els, Cécile A. C. M., additional, and Gorringe, Andrew, additional
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- 2020
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6. Distinct virulence ranges for infection of mice by Bordetella pertussis revealed by engineering of the sensor-kinase BvgS
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Lesne, Elodie, Coutte, Loic, Solans, Luis, Slupek, Stephanie, Debrie, Anne-Sophie, Dhennin, Véronique, Froguel, Philippe, Hot, David, Locht, Camille, Antoine, Rudy, Jacob-Dubuisson, Françoise, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), and Jacob-Dubuisson, Françoise
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Whooping Cough ,Bordetella ,Molecular biology ,[SDV]Life Sciences [q-bio] ,Gene Expression ,lcsh:Medicine ,Protein Engineering ,Pathology and Laboratory Medicine ,Bordetella pertussis ,DISEASE ,ACTIVATION ,Mice ,Sequencing techniques ,Medicine and Health Sciences ,lcsh:Science ,Lung ,Virulence ,VENUS FLYTRAP ,RNA sequencing ,Animal Models ,Genomics ,INTERMEDIATE PHASE ,Bacterial Pathogens ,[SDV] Life Sciences [q-bio] ,Multidisciplinary Sciences ,RECEPTORS ,Experimental Organism Systems ,Medical Microbiology ,Host-Pathogen Interactions ,BACTERIA ,Science & Technology - Other Topics ,Anatomy ,Pathogens ,Transcriptome Analysis ,Research Article ,RESPIRATORY-INFECTION ,Virulence Factors ,General Science & Technology ,Mouse Models ,Nose ,Research and Analysis Methods ,Microbiology ,TRANSDUCTION ,Model Organisms ,Bacterial Proteins ,MD Multidisciplinary ,Genetics ,Animals ,Animal Models of Disease ,Microbial Pathogens ,Science & Technology ,Sequence Analysis, RNA ,MUTATIONS ,Gene Expression Profiling ,lcsh:R ,Organisms ,Biology and Life Sciences ,Computational Biology ,Gene Expression Regulation, Bacterial ,Genome Analysis ,GENE ,Disease Models, Animal ,Animal Models of Infection ,Molecular biology techniques ,Face ,Mutation ,Animal Studies ,lcsh:Q ,Head ,Transcription Factors - Abstract
International audience; The whooping cough agent Bordetella pertussis coordinately regulates the expression of its virulence factors with the two-component system BvgAS. In laboratory conditions, specific chemical modulators are used to trigger phenotypic modulation of B. pertussis from its default virulent Bvg + phase to avirulent Bvg-or intermediate Bvg i phases, in which no viru-lence factors or only a subset of them are produced, respectively. Whether phenotypic modulation occurs in the host remains unknown. In this work, recombinant B. pertussis strains harboring BvgS variants were tested in a mouse model of infection and analyzed using tran-scriptomic approaches. Recombinant BP-Bvg Δ65, which is in the Bvg i phase by default and can be up-modulated to the Bvg + phase in vitro, could colonize the mouse nose but was rapidly cleared from the lungs, while Bvg +-phase strains colonized both organs for up to four weeks. These results indicated that phenotypic modulation, which might have restored the full virulence capability of BP-Bvg Δ65, does not occur in mice or is temporally or spatially restricted and has no effect in those conditions. Transcriptomic analyses of this and other recombinant Bvg i and Bvg +-phase strains revealed that two distinct ranges of virulence gene expression allow colonization of the mouse nose and lungs, respectively. We also showed that a recombinant strain expressing moderately lower levels of the virulence genes than its wild type parent was as efficient at colonizing both organs. Altogether, genetic modifications of BvgS generate a range of phenotypic phases, which are useful tools to decipher host-pathogen interactions.
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- 2018
7. Coiled-Coil Antagonism Regulates Activity of Venus Flytrap-Domain-Containing Sensor Kinases of the BvgS Family
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Lesne, Elodie, Dupré, Elian, Lensink, Marc, Locht, Camille, Antoine, Rudy, Jacob-Dubuisson, Françoise, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), E.L. received a doctoral fellowship from the Region Nord-Pas-de-Calais and INSERM. This work was supported by the Agence Nationale de la Recherche (grant number ANR-13-BSV8-0002-01 to F.J.-D.)., We thank Eva-Maria Krammer for her initial modeling work., ANR-13-BSV8-0002,MECA VENUS,Mécanismes moléculaires de la transduction de signal par BvgS, un modèle de la famille de récepteurs kinases bactériens à domaines Vénus Flytrap(2013), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Jacob-Dubuisson, Françoise, Blanc 2013 - Mécanismes moléculaires de la transduction de signal par BvgS, un modèle de la famille de récepteurs kinases bactériens à domaines Vénus Flytrap - - MECA VENUS2013 - ANR-13-BSV8-0002 - Blanc 2013 - VALID, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-Centre National de la Recherche Scientifique (CNRS)
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MESH: Transcription Factors/metabolism ,MESH: Transcription Factors/chemistry ,sensor kinases ,coiled coil ,Protein Conformation ,two-component regulatory systems ,[SDV]Life Sciences [q-bio] ,Molecular Dynamics Simulation ,BvgS family ,Microbiology ,QR1-502 ,MESH: Bacterial Proteins/metabolism ,Bordetella pertussis ,[SDV] Life Sciences [q-bio] ,MESH: Protein Conformation ,Bacterial Proteins ,MESH: Bacterial Proteins/chemistry ,MESH: Molecular Dynamics Simulation ,Transcription Factors ,Research Article - Abstract
Bordetella pertussis controls the expression of its virulence regulon through the two-component system BvgAS. BvgS is a prototype for a family of multidomain sensor kinases. In BvgS, helical linkers connect periplasmic Venus flytrap (VFT) perception domains to a cytoplasmic Per-Arnt-Sim (PAS) domain and the PAS domain to the dimerization/histidine phosphotransfer (DHp) domain of the kinase. The two linkers can adopt coiled-coil structures but cannot do so simultaneously. The first linker forms a coiled coil in the kinase mode and the second in the phosphatase mode, with the other linker in both cases showing an increase in dynamic behavior. The intervening PAS domain changes its quaternary structure between the two modes. In BvgS homologues without a PAS domain, a helical “X” linker directly connects the VFT and DHp domains. Here, we used BvgS as a platform to characterize regulation in members of the PAS-less subfamily. BvgS chimeras of homologues with natural X linkers displayed various regulation phenotypes. We identified two distinct coiled-coil registers in the N- and C-terminal portions of the X linkers. Stable coil formation in the C-terminal moiety determines the phosphatase mode, similarly to BvgS; in contrast, coil formation in the N-terminal moiety along the other register leads to the kinase mode. Thus, antagonism between two registers in the VFT-DHp linker forms the basis for activity regulation in the absence of the PAS domain. The N and C moieties of the X linker play roles similar to those played by the two independent linkers in sensor kinases with a PAS domain, providing a unified mechanism of regulation for the entire family., IMPORTANCE The whooping cough agent Bordetella pertussis uses the BvgAS sensory transduction two-component system to regulate production of its virulence factors. BvgS serves as a model for a large family of multidomain bacterial sensor kinases. B. pertussis is virulent when BvgS functions as a kinase and avirulent when it switches to phosphatase activity in response to modulating signals. Understanding the molecular regulation of those proteins might lead to new antibacterial strategies. Here, we show that the linker regions between the perception and the enzymatic domains shift between distinct states of conformation in an alternating manner in response to signals and that their antagonistic changes control sensor kinase activity. These linker regions and mechanistic principles appear to be conserved among BvgS homologues, irrespective of the presence or absence of an intervening domain between the perception and the enzymatic domains. This work has thus uncovered general molecular mechanisms that regulate activity of sensor kinases in the BvgS family.
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- 2018
8. La régulation de la virulence de l’agent de la coqueluche Bordetella pertussis : signalisation par le senseur-kinase BvgS
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Lesne, Elodie, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université du Droit et de la Santé - Lille II, and Françoise Jacob-Dubuisson
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Two-component system ,Whooping cough ,Régulation ,Virulence factors ,Virulence ,Système à deux composants ,BvgS ,Coqueluche ,Bordetella pertussis ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Bordetella pertussis is the agent of an acute and highly contagious respiratory disease, whooping cough. In order to colonize the human respiratory tract, this strictly aerobic Gram negative bacterium produces many virulence factors, the expression of which is regulated by the BvgAS two-component system. BvgS is a sensor-kinase composed of three putative domains of perception –two periplasmic Venus flytrap domains and a cytoplasmic PAS domain -, followed by the enzymatic domain and two other domains called phosphotransfert and receiver involved in the phophorelay. The expression of the virulence regulon is activated after the phosphorylation by BvgS of the response regulator BvgA. BvgS is in a kinase mode at the basal state, and the perception of low temperatures or chemical signals like sulfate ions or nicotinate causes a shift to the phosphatase state. The study presented in this manuscript has focused on the characterization of the BvgS sensor-kinase. We have analyzed its putative domains of perception and the mechanisms of signal transduction.Investigations into the dynamics of the periplasmic moiety has provided evidence for a decreasing gradient of dynamics from N to C-terminus at the basal state. Nicotinate binding to the membrane-proximal VFT2 domains decreases the dynamics of the second lobe of VFT1. Tighter interactions between the latter and the VFT2 domain cause a tension on the α helices that precede the transmembrane segments, triggering the transition to the phosphatase state of the enzymatic portion. Perception of modulator by the VFT2 domains –or possibly binding of a ligand in the VFT1 cavity- thus appears to modify periplasmic dynamics, which shifts BvgS activity. We propose that the VFT1 domains are the motor for BvgS activity, and their dynamics are relayed or attenuated by the VFT2 domains. A search for antagonistic VFT1 ligands has been undertaken, along the idea that ligand binding may reduce their dynamics.The VFT and PAS domains, and the PAS and kinase domains are joined to each other by long α helices predicted to form coiled coils. We performed directed mutagenesis and cysteine scanning analyses to decipher signal transduction between the periplasmic domains and the enzymatic moiety of BvgS. The close contacts between the helices of the transmembrane segment are not modified after perception of the modulator, suggesting that signal transduction across the membrane is mediated by symmetrical piston motions. The putative coiled coil before the PAS domain shows rotational dynamics at the basal state. Modulator perception causes the helices to splay, and this motion may modify the PAS domains interface. Our topology analyses of the PAS domain confirm that changes occur at this interface between the kinase and phosphatase states of BvgS. Finally, the coiled coil between the PAS and kinase domains presents a strong rotational dynamics at the basal state, which is consistent with the model of regulation of kinase activity proposed for other sensor-kinases. After perception of a modulator, this coiled coil becomes more rigid, allowing the shift to the phosphatase state. The occurrence of two states of dynamics for this coiled coil has also been demonstrated in the absence of the PAS domain.These studies have advanced our understanding of BvgS and allow us to propose a model of signaling by this sensor-kinase, which may apply more broadly to other family members.; Bordetella pertussis est l’agent responsable de la coqueluche. Pour coloniser le tractus respiratoire humain, cette bactérie à Gram négatif, aérobie stricte, produit de nombreux facteurs de virulence dont l’expression est sous la dépendance du système à deux composants BvgAS. BvgS est un senseur-kinase dimérique. Chaque monomère est constitué de trois domaines putatifs de perception - deux domaines Venus flytrap périplasmiques et un domaine PAS cytoplasmique -, suivis du domaine enzymatique et deux autres domaines, de phospho-transfert et receveur, impliqués dans la cascade de phosphorylation. L’expression du régulon de virulence est activée suite à la phosphorylation par BvgS du régulateur de réponse BvgA. BvgS est en mode kinase à l’état basal, et la perception de basses températures ou de signaux chimiques comme les ions sulfate ou nicotinate cause son passage en mode phosphatase. L’étude présentée dans ce manuscrit vise à caractériser le senseur-kinase BvgS en analysant les domaines putatifs de perception ainsi que la transduction de signal qui s’effectue au sein de la molécule. L’étude de la portion périplasmique a permis de mettre en évidence, à l’état basal, un gradient de dynamique décroissant. En se fixant au domaine VFT2 proximal à la membrane, le nicotinate induirait une diminution de la dynamique du second lobe du VFT1, causée par la formation d’un bloc compact entre le domaine VFT2 et le deuxième lobe du domaine VFT1. Cette rigidification exercerait une tension sur les hélices α qui précèdent les segments transmembranaires, provoquant une transition de la portion cytoplasmique vers l’état phosphatase. La perception de modulateurs par le domaine VFT2 - ou possiblement la fixation d’un ligand dans la cavité du VFT1- modifierait cette dynamique et causerait le changement d’activité de BvgS. Ainsi, nous proposons un modèle dans lequel le VFT1 est considéré comme le moteur du système, lui impulsant une dynamique qui serait relayée ou atténuée par le domaine VFT2. Une recherche de ligands antagonistes pour le domaine VFT1 a été entreprise, selon l’idée que la fixation d’un ligand réduirait la dynamique de ce dernier. Au sein du dimère, des connecteurs prédits pour former des enroulements d’hélices α (‘coiled coil’) relient entre eux les domaines VFT et PAS, et les domaines PAS et kinase de BvgS. La transduction d’information entre les domaines périplasmiques et le site enzymatique de BvgS a été analysée par mutagénèse dirigée et ‘cysteine scanning’. Des contacts proches sont observés entre les hélices constituant le segment transmembranaire, qui ne semblent pas être modifiés après perception de modulateur. Nous suggérons donc un modèle de piston symétrique pour la transmission d’information au travers de la membrane. Le coiled coil putatif précédant le domaine PAS présente une certaine dynamique rotationnelle à l’état basal. La perception de modulateurs semble induire l’écartement de ces hélices, ce qui pourrait permettre un changement de l’interface des domaines PAS. L’étude de la topologie du domaine PAS confirme une modification de cette interface entre les modes kinase et phosphatase de BvgS. Enfin, le coiled coil reliant les domaines PAS et kinase est sujet à une forte dynamique rotationnelle à l’état basal, en accord avec un modèle de régulation de l’activité kinase proposé dans d’autres systèmes. Suite à la perception de modulateur, une rigidification marquée de ce coiled coil est observée, permettant le passage en mode phosphatase. L’existence de deux états dynamiques différents de ce coiled coil a également été mise en évidence en absence du domaine PAS.Ces études ont permis d’avancer dans la compréhension de BvgS et de proposer un modèle de la signalisation au sein de ce senseur-kinase, qui pourrait s’appliquer aux autres membres de la famille de BvgS.
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- 2016
9. Conformational Changes of an Interdomain Linker Mediate Mechanical Signal Transmission in Sensor Kinase BvgS
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Lesne, Elodie, primary, Dupré, Elian, additional, Locht, Camille, additional, Antoine, Rudy, additional, and Jacob-Dubuisson, Françoise, additional
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- 2017
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10. Characterization of a Bvg-regulated fatty acid methyl-transferase in Bordetella pertussis
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Rivera-Millot, Alex, primary, Lesne, Elodie, additional, Solans, Luis, additional, Coutte, Loic, additional, Bertrand-Michel, Justine, additional, Froguel, Philippe, additional, Dhennin, Véronique, additional, Hot, David, additional, Locht, Camille, additional, Antoine, Rudy, additional, and Jacob-Dubuisson, Françoise, additional
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- 2017
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11. Signal transduction by BvgS sensor kinase. BINDING OF MODULATOR NICOTINATE AFFECTS THE CONFORMATION AND DYNAMICS OF THE ENTIRE PERIPLASMIC MOIETY.
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Dupré, Elian, primary, Lesne, Elodie, additional, Guérin, Jérémy, additional, Lensink, Marc F., additional, Verger, Alexis, additional, de Ruyck, Jérôme, additional, Brysbaert, Guillaume, additional, Vezin, Hervé, additional, Locht, Camille, additional, Antoine, Rudy, additional, and Jacob-Dubuisson, Françoise, additional
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- 2015
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12. Translocation path of a substrate protein through its Omp85 transporter
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Baud, Catherine, primary, Guérin, Jérémy, additional, Petit, Emmanuelle, additional, Lesne, Elodie, additional, Dupré, Elian, additional, Locht, Camille, additional, and Jacob-Dubuisson, Françoise, additional
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- 2014
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13. Continuous processing of skim milk by a combination of pulsed electric fields and conventional heat treatments: does a synergetic effect on microbial inactivation exist?
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Floury, Juliane, primary, Grosset, Noël, additional, Lesne, Elodie, additional, and Jeantet, Romain, additional
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- 2006
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14. Generation of a Universal Human Complement Source by Large-Scale Depletion of IgG and IgM from Pooled Human Plasma.
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Alexander F, Brunt E, Humphries H, Cavell B, Leung S, Allen L, Halkerston R, Lesne E, Penn E, Thomas S, Gorringe A, and Taylor S
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- Chromatography, Affinity, Humans, Immunoglobulin G, Immunoglobulin M, Complement System Proteins immunology
- Abstract
Complement is a key component of functional immunological assays used to evaluate vaccine-mediated immunity to a range of bacterial and viral pathogens. However, standardization of these assays is complicated due to the availability of a human complement source that lacks existing antibodies acquired either through vaccination or natural circulation of the pathogen of interest. We have developed a method for depleting both IgG and IgM in 200 mL batches from pooled hirudin-derived human plasma by sequential affinity chromatography using a Protein G Sepharose column followed by POROS™ CaptureSelect™ IgM Affinity resin. The production of large IgG- and IgM-depleted batches of human plasma that retains total hemolytic and alternative pathway activities allows for improved assay standardization and comparison of immune responses in large clinical trials., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
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- 2022
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15. Structural insight into the role of the PAS domainfor signal transduction in sensor-kinase BvgS.
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Dupré E, Clantin B, Yuan Y, Lecher S, Lesne E, Antoine R, Villeret V, and Jacob-Dubuisson F
- Abstract
The two-component system BvgAS controls the virulence regulon in Bordetella pertussis BvgS is the prototype of a family of sensor histidine-kinases harboring periplasmic Venus flytrap (VFT) domains. The VFT domains are connected to the cytoplasmic kinase moiety by helical linkers separated by a Per-ARNT-Sim (PAS) domain. Antagonism between the two linkers, as one forms a coiled coil when the other is dynamic and vice versa, regulates BvgS activity. Here we solved the structure of the intervening PAS domain by X-ray crystallography. Two forms were obtained that notably differ by the connections between the PAS core domain and the flanking helical linkers. Structure-guided mutagenesis indicated that those connections participate in the regulation of BvgS activity. The PAS domain thus appears to function as a switch-facilitator module whose conformation determines the output of the system. As many BvgS homologs have similar architectures, the mechanisms unveiled here are likely to generally apply to the regulation of sensor-histidine kinases of that family. IMPORTANCE The whooping cough agent Bordetella pertussis colonizes the human respiratory tract using virulence factors co-regulated by the sensory transduction system BvgAS. BvgS is a model for a family of sensor-kinase proteins, some of which are found in important bacterial pathogens. BvgS functions as a kinase or a phosphatase depending on external signals, which determines if B. pertussis is virulent or avirulent. Deciphering its mode of action might thus lead to new ways of fighting infections. Here we used X-ray crystallography to solve the three-dimensional structure of the domain that precedes the enzymatic moiety and identified features that regulate BvgS activity. As many sensor-kinases of the BvgS family harbor homologous domains, the mechanism unveiled here might be of general relevance., (Copyright © 2021 American Society for Microbiology.)
- Published
- 2021
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